CONICET | Buscador de Institutos y Recursos Humanos

Intratumoral heterogeneity, in part due to the presence of highly resistant cancer cells usually associated with increased stemeness, as well as the toxicity to non-cancer cells are key factors that limit the effectiveness of chemotherapy [1]. We recently found that Nigericin is able to decreased the viability of highly resistant lung cancer cells[2]. The aim of this work was to evaluate the anticancer activity of Nigericin (NG) + Sorafenib (SF) in lung cancer cells growing under adherent conditions (ACs, Anchorage-dependent) and floating (FTs, anchorage-independent) conditions. Adherent human H460 lung cancer cell line was grown following routine culture conditions. FTs were prepared by plating cells in ultra-low attachment plates for at least 7 days. FTs are higly resitant to several conventional anticancer drugs and therefore are excellent in vitro models of chemoresitance[3]. ACs and FTs were treated with NG, SF or both for 72 hours and the viability was measured by the MTT or CCK assay respectively. Clonogenicity was determined by the Colony Forming Assay (CFA). Both drugs at single agents decreased the viability of H460 in a concentration dependent manner with IC50 of approximately 1 M and 5 M, respectively. These IC50 values were tested in combination and were found to be more potent compared to each single drug. Similar results were obtained with the A549 lung cancer cell line. Both drugs as single agents or in combination decreased the clonogenicity of A549 cells (determined by the colony forming assay) to a similar extent.The combinatory anticancer effect of NG+SF has the potential to eliminate highly resistant lung cancer cells and further studies are needed to advance studies in animal models. While the concentration of SF used in this study is within the therapeutic range the pharmacokinetic of NG has not been characterized. We are currently developing NG-loaded nanoparticles to selectively deliver NG to cancer cells.

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